title: Incidence and risk of treatment-related mortality in cancer patients treated with EGFR-TKIs: a meta-analysis of 22 phase III randomized controlled trials.
abstract: Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) have become the cornerstone in the treatment of lung cancers that harbor EGFR mutations, but also play an important role in the treatment of other lung cancers and have been investigated among various types of solid tumors. However, these drugs have been associated with an increase in the risk of potentially life-threatening adverse event, such as arterial and venous thrombotic events. We performed a meta-analysis to determine the incidence and risk of fatal adverse events (FAEs) in cancer patients treated with EGFR-TKIs. Incidence rates, relative risks (RRs), and 95% confidence intervals (CIs) were calculated using a random effects model. A total of 13,825 patients from 22 trials were included. Among patients treated with EGFR-TKIs, the overall incidence of FAEs was 1.9% (95%CI: 1.2-2.9%), and the risk of FAEs was 0.99 (95%CI: 0.70-1.41, p = 0.97). No increase in FAEs was detected in any prespecified subgroup. Additionally, using EGFR-TKIs as salvage treatment significantly reduced the risk of FAEs when compared to the controls (RR 0.51, 95%CI: 0.29-0.87, p = 0.013). In conclusion, this analysis suggests that the use of EGFR-TKIs does not increase the risk of FAEs in patients with advanced solid tumors, and EGFR-TKIs are safety and tolerable for cancer patients, especially for those previously treated patients.
authors.affiliation: Department of Oncology, The Sixth People's Hospital, Shanghai Jiao Tong University, No. 600, Yishan Road, Shanghai 200233, China.
authors.forename: Wei-Xiang
authors.initials: WX
authors.lastname: Qi
authors.forename: Li-Na
authors.initials: LN
authors.lastname: Tang
authors.forename: Ai-Na
authors.initials: AN
authors.lastname: He
authors.forename: Yang
authors.initials: Y
authors.lastname: Yao
authors.forename: Zan
authors.initials: Z
authors.lastname: Shen
mesh_terms: D000970:Antineoplastic Agents / Q000009:adverse effects*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects; D001650:Bile Duct Neoplasms / Q000188:drug therapy / Q000401:mortality; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000401:mortality; D017326:Clinical Trials, Phase III as Topic; D066246:ErbB Receptors / Q000037:antagonists & inhibitors*; D000069347:Erlotinib Hydrochloride; D000077156:Gefitinib; D006258:Head and Neck Neoplasms / Q000188:drug therapy / Q000401:mortality; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000401:mortality; D009369:Neoplasms / Q000188:drug therapy* / Q000401:mortality; D010190:Pancreatic Neoplasms / Q000188:drug therapy / Q000401:mortality; D047428:Protein Kinase Inhibitors / Q000009:adverse effects*; D011799:Quinazolines / Q000008:administration & dosage / Q000009:adverse effects; D016032:Randomized Controlled Trials as Topic; D012307:Risk Factors
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D000069347:Erlotinib Hydrochloride; D066246:ErbB Receptors; D000077156:Gefitinib
keywords: Cancer; EGFR-TKIs; Erlotinib; Fatal adverse events; Gefitinib; Meta-analysis